The high number of US military forces suffering from traumatic brain injury (TBI) in the current wars in Iraq and Afghanistan can be directly related to an increase in blast exposures. It has been concluded that a greater proportion of head and neck injuries were documented in these theaters than in any previous conflict. Explosives accounted for 78% of these injuries, the highest proportion reported for any large scale conflict. The number of reports linking mild TBI to blast overpressure exposure has been rising as a result. Mild TBI (mTBI) is associated with headaches, and memory and sleep disturbances. These problems may persist and can prolong recovery from co-morbid conditions. To better understand the effects of blast overpressure on the brain, our group has developed a rodent model of blast neurotrauma. Reports indicate that low levels of overpressure exposure can induce cognitive and histological alterations, demonstrating central nervous system involvement. However, the relationship between neurobiology and neuropsychology after blast injury is unclear and progress has been hampered by the lack of collaboration between basic scientists and neuropsychologists and of animal models that reflect human outcomes. Thus, the long range objective of our team of bioengineers, neuroscientists and neuropsychologists is to identify behavioral and cognitive assessments that will define blast neurotrauma and predict recovery patterns after blast exposure. We hypothesize that blast energy transmission to the brain causes damage at the cellular level which results in measureable behavioral and cognitive changes. This pilot study will provide a better characterization our rodent blast neurotrauma model and will help clarify the injury mechanism from blast exposure. We will investigate which cellular cascades and neurocognitive/behavioral changes are indicators for blast neurotrauma injury. Our Specific Aims are to (1) refine a series of behavioral and neurocognitive impairment tests to closely model impairment observed in military personnel exposed to blast neurotrauma, and to (2) utilize histological methods to guide investigation of cellular/molecular mechanisms likely to underlie brain cellular damage from blast neurotrauma. At the conclusion of this pilot study, we expect to have confirmed and further developed an experimental animal model of blast neurotrauma. We expect to demonstrate an association between blast-related neuropathology and neurocognitive/behavioral changes. Progress toward a highly reliable experimental model that accurately represents the clinical problems of Veterans with blast TBI will aid in the development of effective diagnostic and treatment regimes that are currently lacking and impeding maximal recovery of our Veterans. PUBLIC HEALTH RELEVANCE: Closed head injuries are out-numbering penetrating injuries among military personnel seen at the Walter Reed Army Medical Center. It has been reported that a majority of blast exposed soldiers admitted to the hospital had been given a diagnosis of TBI, with a significant number identified as mild TBI. Since all classes of TBI can develop into chronic conditions, this research will have an enormous impact on our Veterans and the health care needed to serve them. Furthermore, blast-induced mTBI manifests itself by presenting numerous symptoms, which will expand the diagnostic duties of the clinician. By developing appropriate animal models that accurately represent the human outcomes of chronic mTBI, we can progress to design more effective therapeutic agents to better serve our Veterans.